The work leading to this invention has received funding from the European Community's Seventh Framework Programme FP7/2007-2013/under grant agreement No HEALTH-F5-2008-200755.
Chronic lymphocytic leukaemia (CLL) is a white blood cell cancer that is characterised by an abnormal neoplastic proliferation of B lymphocyte cells (B cells). The B cells of CLL differ from normal B cells in their activation and maturation stage and are in particular derived from antigen experienced B cells with different immunoglobulin heavy chain variable (IgVH) gene mutations (Chiorazzi N et al., N Engl J Med 2005; 352:804-15). CLL patients with mutated IgVH genes have a better prognosis compared to patients with unmutated genes (Damle R N et al., Blood 1999; 94:1840-7; Hamblin T J et al., Blood 1999; 94:1848-54).
Global gene expression profiling studies have revealed partly distinguishing but in general overlapping expression profiles in mutated and unmutated leukaemic B cells, suggesting a common phenotype (Klein U et al., J Exp Med 2001; 194:1625-38; Rosenwald A et al., J Exp Med 2001; 194:1639-47).
Gene expression profiling studies have shown a 43.8 fold increase of the orphan receptor tyrosine kinase (RTK) ROR1 in CLL cells (Klein U et al., J Exp Med 2001; 194:1625-38). Ror1 is a member of the RTK family of orphan receptors related to muscle specific kinase (MUSK) and Trk neurotrophin receptors (Glass D J, et al., Cell 1996; 85:513-23; Masiakowski P et al., J Biol Chem 1992; 267:26181-90; Valenzuela D M et al., Neuron 1995; 15:573-84).
Ror receptors are cell surface receptors participating in signal transduction, cell-cell interaction, regulation of cell proliferation, differentiation, cell metabolism and survival (Masiakowski P et al., Biol Chem 1992; 267:26181-90; Yoda A et al., J Recept Signal Transduct Res 2003; 23:1-15). They are evolutionarily highly conserved between different species e.g. human, mouse, Drosophila, and C. elegans. 
The human ROR1 gene has a coding region of 2814 bp with a predicted 937 amino acids sequence and 105 kDa protein size including an Ig-like domain, cysteine-rich domain, kringle domain, tyrosine kinase domain, and proline-rich domain (FIG. 1) (Yoda A et al., J Recept Signal Transduct Res 2003; 23:1-15).
ROR1 is located on chromosomal region 1p31.3 (http://www.ensembl.org), a region where chromosomal aberrations are not frequently seen in haematological malignancies (FIG. 2). The human ROR1 is expressed in heart, lung, and kidney but less in placenta, pancreas and skeletal muscles (Reddy U R et al., Oncogene 1996; 13:1555-9). ROR1 was originally cloned from a neuroblastoma cell line (Masiakowski P et al., J Biol Chem 1992; 267:26181-90) and subsequently a shorter form lacking the entire extracellular domain but containing the transmembrane domain was isolated from a foetal brain library. Truncated Ror1 (t-Ror1) gene has been reported in foetal and adult human central nervous system, in human leukaemias, lymphoma cell lines, and in a variety of human cancers derived from neuroectoderm (Reddy U R et al., Oncogene 1996; 13:1555-9). A shorter transcript from exons 1-7 including a short part of intron 7 has also been described with a predicted length of 393 amino acids and a molecular weight of 44 kDa (Ensembl ID; ENSG00000185483).
The expression of ROR-1 in cancer cells has been described for CLL (Baskar et al (2008) Clin Cancer Res, 14, p 396-404; Choudhury et al (2010) B. J. Haem, 151, p327-335; and Hudecek et al (2010) Blood, online publication DOI: 10.1182/blood-2010-05-283309); MCL (Hudecek (2010)); B-ALL (Hudecek (2010) and Shabani at al (2008) Leuk & Lymph, 49 p1360-1367), other leukaemias and lymphomas (Fakuda et al (2008) PNAS, 105, p3047-3052; and Barna et al (2010) Hematol Oncol, online publication DOI: 10-1002/hon.948) and solid cancers (renal and colon) (Katoh & Kotoh (2005) Oncol Rep 14, p1381-4).